Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

Background-IgG and Ige subclass antibodies to Aspergillus fumigatus (A fumi gatus) were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic bronchopulm onary aspergillosis(ABPA). Methods-An ELISA technique using water soluble somatic hyphal (WSSH) A fumi gatus antigens and subclass specific monoclonal antibodies was used for cro ss sectional quantification of IgG and IgG(1-4) subclass antibody levels in the serum of 238 patients with cystic fibrosis and 107 healthy controls. Results-In patients with cystic fibrosis persistently colonised with A fumi gatus the subclass antibody levels were significantly increased compared wi th patients with cystic fibrosis never or rarely colonised (p<0.001). The g roup of patients persistently colonised with A fumigatus with ABPA (+Af+ABP A) had significantly increased levels of IgG antibodies to A fumigatus (Af- IgG) (median 69 ELISA units (EU) versus 31) and of subclasses Af-IgG(1) (91 versus 27), Af-IgG(2) (143 versus 56), and Af-IgG(4) antibodies (72 versus 20), but not of IgG(3) (17 versus 15), compared with the colonised patient s without ABPA (+Af-ABPA). Patients with cystic fibrosis with no or only ra re isolates A fumigatus without ABPA (-Af-ABPA) also had significantly incr eased subclass antibody levels (Af-IgG(1) 9 versus 3, Af-IgG(2) 28 versus 5 , Af-IgG(4) 16 versus 4; p<0.001) compared with healthy controls. Low, alth ough detectable, levels of antibodies were demonstrated in healthy controls . ABPA seemed to occur independently of Pseudomonas aeruginosa infection. U sing diagnostic cut off levels for ABPA, sensitivity and specificity were c alculated. The highest specificity was found for IgG(4) (88%); sensitivity was between 65% and 73%. The positive predictive values (PPV) were moderate , whereas the negative predictive values (NPV) were high (96% in all subcla sses except IgG(3) with 94%), PPV increased to 50% if IgG(1) as well as IgG (2) and IgG(4) were included. Conclusions-In a large number of unselected patients with cystic fibrosis s ignificantly increased levels of Af-specific antibodies belonging to total IgG and all four subclasses were found in all groups of patients compared w ith healthy controls. In patients persistently colonised with A fumigatus t hese levels were significantly higher than in non-colonised patients, and t he significantly highest levels (with the exception of IgG(3)) were found i n patients with ABPA. Using a sensitive ELISA technique, measurements of Ig G and IgG subclass antibodies to A fumigatus might be of importance in the management of ABPA, especially as a screening test to exclude the presence of ABPA; other tests are needed to confirm the diagnosis.